This pilot, phase I trial studies the side effects and best dose of bortezomib in treating patients with acquired immune deficiency syndrome (AIDS)-related Kaposi sarcoma that has come back or has not responded to treatment. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

MTD based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: 56 days ] [ Designated as safety issue: Yes ]

MTD is defined as the highest assigned dose at which < 2 patients (out of 6) experience dose-limiting toxicity. Adverse events will be summarized by type, timing, and severity grade.

Secondary Outcome Measures:

Change in lytic gene expression [ Time Frame: Baseline to 1 year ] [ Designated as safety issue: No ]

The association between change in lytic gene expression with clinical response of KS tumors will be investigated with exact logistic regression. Hierarchical clustering will be used to explore if gene expression patterns differ according to clinical response.

Changes in bortezomib in KSHV copy number in PBMC and plasma [ Time Frame: Baseline to 1 year ] [ Designated as safety issue: No ]

Analyzed using the Wilcoxon signed rank test. The association between change in KSHV copy number with clinical response of KS tumors will be investigated with exact logistic regression.

Changes in viral antigen expression in biopsy specimens [ Time Frame: Baseline to 1 year ] [ Designated as safety issue: No ]

Spearman's rank correlations will be calculated to examine whether the changes in KSHV viral copy number in PBMC and plasma occur in concert or independently with changes in viral antigen expression in biopsy specimens collected at baseline, day 2 and treatment discontinuation.

Clinical KS response rates based on the Response Evaluation Criteria in Solid Tumors [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

Exact binomial 95% confidence intervals will be computed. Descriptive statistics will also be presented for complete and partial response rates.

Patients receive bortezomib intravenously (IV) on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks and then every 3 months for up to 1 year.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Adult patients with cutaneous AIDS-related biopsy-proven KS relapsed after or refractory to at least one other prior systemic therapy

Patients must have cutaneous KS lesion(s) amenable to biopsy (either one lesion >= 12 mm or 3 >= 4 mm) in addition to at least 5 lesions measurable for assessment; all of these lesions must not have been previously radiated

Must have been on stable anti-retroviral therapy for at least 12 weeks with a principal investigator (PI)-based or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen of at least three drugs, with no intention to change the regimen for the duration of the study; patients who have a high likelihood of better HIV management with a new antiretroviral regimen should defer enrollment until the changes are in place and the new highly active antiretroviral therapy (HAART) regimen meets the 12 week criteria

Serologic documentation of HIV infection at any time prior to study entry, as evidenced by positive enzyme-linked immunosorbent assay (ELISA), positive western blot, or other Food and Drug Administration (FDA)-approved licensed HIV test, or a detectable blood level of HIV RNA

Women of child-bearing potential must have a negative pregnancy test within 72 hours before initiation of study drug dosing; post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential; male and female subjects of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug; (Note: a woman of childbearing potential is one who is biologically capable of becoming pregnant; this includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives)

Hemoglobin >= 8.0 gm/dL; subjects may be receiving growth factor support to meet these criteria

Platelets >= 100,000/mm^3

Total bilirubin =< 1.5 mg/dL; if the elevated bilirubin is felt to be secondary to indinavir or atazanavir therapy, then subjects will be allowed on protocol without any limit on the total bilirubin if the direct bilirubin is normal

Herpes zoster (shingles) outbreak within the last 6 months or inability to take herpes zoster prophylaxis

Patient is =< 5 years free of another primary malignancy except if the other primary malignancy is neither currently clinically significant nor requiring active intervention, or if the other primary malignancy is a localized squamous or basal cell skin cancer or cervical/anal carcinoma in situ

Acute treatment for an infection or other serious medical illness within 14 days prior to study entry

Patients may not have had anti-neoplastic treatment for Kaposi sarcoma (including chemotherapy, radiation therapy, biological therapy, or investigational therapy) within 4 weeks (6 weeks for nitrosourea or mitomycin-C) of study treatment

Prior treatment with bortezomib or other investigational proteasome inhibitors

Previous local therapy of any KS indicator lesion within 60 days, unless the lesion has clearly progressed with enlargement since the local therapy

Use of any investigational drug or treatment within 4 weeks prior to randomization

Physical or psychiatric conditions that in the estimation of the investigator place the patient at high risk of toxicity or non-compliance

Hypersensitivity to boron

Subjects with grade III/IV cardiac disease as defined by the New York Heart Association criteria. (e.g., congestive heart failure, myocardial infarction within 6 months of study)

Subject has an acute or known chronic liver disease (e.g., chronic active hepatitis, cirrhosis); subjects with known hepatitis B or C infection may be enrolled if they have either documentation of no or minimal fibrosis on liver biopsy or undetectable hepatitis virus on polymerase chain reaction (PCR)

Systemic corticosteroid treatment, other than replacement doses

Female subjects who are pregnant or breast-feeding

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01016730